6-week study treatment to evaluate the safety and effectiveness of AZD2066 in patients with major depressive disorder

Study identifier:D0475C00020

ClinicalTrials.gov identifier:N/A

EudraCT identifier:N/A

CTIS identifier:N/A

Terminated/Withdrawn

Official Title

A Phase IIa, Multi-centre, Randomized, Double-Blind, Double-Dummy, Active and Placebo Controlled, parallel Group Study to Assess the Effectiveness and Safety of AZD2066 after 6 weeks of treatment in Patients with Major Depressive Disorder - D0475C00020

Medical condition

Major depressive disorder

Phase

Phase 2

Healthy volunteers

Study drug

AZD2066, Placebo, Duloxetine

Sex

All

Actual Enrollment

131

Study type

Interventional

Age

18 Years - 65 Years

Date

Study Start Date: 01 May 2010

Primary Completion Date: 01 Nov 2010

Study Completion Date: 01 Nov 2010

Study design

Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind
Primary Purpose: Treatment

Verification:

Verified 01 Sept 2012 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Location

Research Site

GARDEN GROVE, CA, United States

Location

Research Site

SAN DIEGO, CA, United States

Location

Research Site

JACKSONVILLE, FL, United States

Location

Research Site

ATLANTA, GA, United States

Location

Research Site

ROCKVILLE, MD, United States

Location

Research Site

BOSTON, MA, United States

Location

Research Site

CEDARHURST, NY, United States

Location

Research Site

ROCHESTER, NY, United States

Arms	Assigned Interventions
Experimental: AZD2066	Drug: AZD2066 18 mg once daily
Placebo Comparator: Placebo	-
Active Comparator: Duloxetine Duloxetine	Drug: Duloxetine 60 mg once daily

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
This study was conducted only in the United States (US). A total of 13 study centers enrolled 249 patients. First subject enrolled: 27 May 2010 Last subject last visit: 10 November 2010

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Patients with major depressive disorder were included.

Reporting Groups

	Description
AZD2066	AZD2066 12 mg, 18 mg
Duloxetine	Duloxetine 30 mg, 60 mg
Placebo	Placebo

Participant Flow: Overall Study

	AZD2066	Duloxetine	Placebo
STARTED	40	47	44
COMPLETED	20	19	19
NOT COMPLETED	20	28	25
Adverse Event	2	4	2
Withdrawal by Subject	2	2	2
Lost to Follow-up	2	3	1
Protocol Violation	0	3	1
Study Closure	14	14	17
Lack of Efficacy	0	1	0
Patient could not swollow medication	0	0	1
Withdrawal by Subject	0	0	1
Positive urine ethanol	0	1	0

Baseline Characteristics

Analysis Population Description -- Explanation of how the number of participants for analysis was determined.

Reporting Groups

	Description
AZD2066	AZD2066 12 mg, 18 mg
Duloxetine	Duloxetine 30 mg, 60 mg
Placebo	Placebo

Baseline Measures

	AZD2066	Duloxetine	Placebo	Total
Number of Participants [units: Participants]	40	47	44	131
Age Continuous [units: Years] Mean ( Full Range )	42.2 (21 to 60)	39.9 (19 to 60)	38.4 (20 to 61)	40.1 (19 to 60)
Gender, Male/Female [units: Participants]
Female	23	24	30	77
Male	17	23	14	54

Outcome Measures

1. Primary Outcome Measure: MADRS total score change from baseline to Week 6 [ Time Frame: 6 weeks ]

Measure Type	Primary
Measure Name	MADRS total score change from baseline to Week 6
Measure Description	Montgomery-Asberg Depression Rating Scale (MADRS): The MADRS is a 10-item scale for the evaluation of depressive symptoms (Montgomery et al 1979). Each MADRS item is rated on a 0 to 6 scale. Total score range from 0-60, where higher MADRS scores indicate higher levels of depressive symptoms.
Time Frame	6 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD2066	AZD2066 12 mg, 18 mg
Duloxetine	Duloxetine 30 mg, 60 mg
Placebo	Placebo

Measured Values

	AZD2066	Duloxetine	Placebo
Number of Participants Analyzed [units:participants]	39	45	40
MADRS total score change from baseline to Week 6 [units: scores on the scale] Mean (Standard Deviation)	-13.1658 (2.11)	-14.0271 (1.97)	-14.1575 (2.16)

No statistical analysis provided for MADRS total score change from baseline to Week 6

2. Secondary Outcome Measure: MADRS response [ Time Frame: 6 weeks ]

Measure Type	Secondary
Measure Name	MADRS response
Measure Description	A MADRS responder at week 6 is defined as a patient with a reduction of at least 50% from baseline MADRS total score.
Time Frame	6 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD2066	AZD2066 12 mg, 18 mg
Duloxetine	Duloxetine 30 mg, 60 mg
Placebo	Placebo

Measured Values

	AZD2066	Duloxetine	Placebo
Number of Participants Analyzed [units:participants]	21	20	19
MADRS response [units: Participants]	9	9	9

No statistical analysis provided for MADRS response

3. Secondary Outcome Measure: MADRS remission [ Time Frame: 6 weeks ]

Measure Type	Secondary
Measure Name	MADRS remission
Measure Description	A patient will be classified as in remission if their MADRS total score is ≤10 at Week 6
Time Frame	6 weeks
Safety Issue?	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Reporting Groups

	Description
AZD2066	AZD2066 12 mg, 18 mg
Duloxetine	Duloxetine 30 mg, 60 mg
Placebo	Placebo

Measured Values

	AZD2066	Duloxetine	Placebo
Number of Participants Analyzed [units:participants]	21	20	19
MADRS remission [units: Participants]	5	8	7

No statistical analysis provided for MADRS remission

Serious Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Reporting Groups

	Description
AZD2066	AZD2066 12 mg, 18 mg
Duloxetine	Duloxetine 30 mg, 60 mg
Placebo	Placebo

Serious Adverse Events

AZD2066

Duloxetine

Placebo

Total, serious adverse events

# participants affected / at risk

1/40 (2.50%)

0/47 (0.00%)

0/44 (0.00%)

Reproductive system and breast disorders

Ovarian mass¹,^†

# participants affected / at risk

1/40 (2.50%)

0/47 (0.00%)

0/44 (0.00%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 13.1
2	Term from vocabulary,

Other Adverse Events

Time Frame	No text entered.
Additional Description	No text entered.

Frequency Threshold

Threshold above which other adverse events are reported	5%

Reporting Groups

	Description
AZD2066	AZD2066 12 mg, 18 mg
Duloxetine	Duloxetine 30 mg, 60 mg
Placebo	Placebo

Other Adverse Events

AZD2066

Duloxetine

Placebo

Total, other (not including serious) adverse events

# participants affected / at risk

21/40 (52.50%)

30/47 (63.83%)

16/44 (36.36%)

Gastrointestinal disorders

NAUSEA¹,^†

# participants affected / at risk

6/40 (15.00%)

12/47 (25.53%)

4/44 (9.09%)

Gastrointestinal disorders

DIARRHOEA¹,^†

# participants affected / at risk

3/40 (7.50%)

10/47 (21.28%)

4/44 (9.09%)

Gastrointestinal disorders

DRY MOUTH¹,^†

# participants affected / at risk

1/40 (2.50%)

7/47 (14.89%)

4/44 (9.09%)

Gastrointestinal disorders

CONSTIPATION¹,^†

# participants affected / at risk

4/40 (10.00%)

1/47 (2.13%)

3/44 (6.82%)

Gastrointestinal disorders

ABDOMINAL PAIN¹,^†

# participants affected / at risk

2/40 (5.00%)

0/47 (0.00%)

0/44 (0.00%)

Gastrointestinal disorders

DYSPEPSIA¹,^†

# participants affected / at risk

2/40 (5.00%)

0/47 (0.00%)

0/44 (0.00%)

General disorders and administration site conditions

IRRITABILITY¹,^†

# participants affected / at risk

2/40 (5.00%)

0/47 (0.00%)

1/44 (2.27%)

Infections and infestations

UPPER RESPIRATORY TRACT INFECTION¹,^†

# participants affected / at risk

4/40 (10.00%)

3/47 (6.38%)

1/44 (2.27%)

Metabolism and nutrition disorders

INCREASED APPETITE¹,^†

# participants affected / at risk

2/40 (5.00%)

0/47 (0.00%)

1/44 (2.27%)

Nervous system disorders

HEADACHE¹,^†

# participants affected / at risk

10/40 (25.00%)

7/47 (14.89%)

0/44 (0.00%)

Nervous system disorders

SOMNOLENCE¹,^†

# participants affected / at risk

2/40 (5.00%)

5/47 (10.64%)

0/44 (0.00%)

Nervous system disorders

DIZZINESS¹,^†

# participants affected / at risk

3/40 (7.50%)

3/47 (6.38%)

2/44 (4.55%)

Psychiatric disorders

INSOMNIA¹,^†

# participants affected / at risk

4/40 (10.00%)

2/47 (4.26%)

0/44 (0.00%)

Psychiatric disorders

ANXIETY¹,^†

# participants affected / at risk

2/40 (5.00%)

0/47 (0.00%)

2/44 (4.55%)

Reproductive system and breast disorders

ERECTILE DYSFUNCTION¹,^†

# participants affected / at risk

0/40 (0.00%)

5/47 (10.64%)

1/44 (2.27%)

Skin and subcutaneous tissue disorders

RASH¹,^†

# participants affected / at risk

2/40 (5.00%)

1/47 (2.13%)

0/44 (0.00%)

†	Events were collected by systematic assessment
1	Term from vocabulary, MedDRA 13.1
2	Term from vocabulary,

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days . The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: No publication or presentation of results until the earlier of 1) the date of the first study results publication or 2) 18 months after completion or termination of the study. AZ review 60 days prior submission and AZ has the possibility to further delay publication for an additional 90 days

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact

Name/Title:	Gerard Lynch
Organization:	AstraZeneca
Phone	645895 Ext: +44 1509
E-mail:	[email protected]

Documents available

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=230&filename=CSR-D0475C00020.pdf
Download
CSR-D0475C00020.pdf
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Study Information

800-236-9933

information.center@astrazeneca.com

Investigators

Principal Investigator

Richard Malamut

AstraZeneca

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

Research Site

https://filehosting.pharmacm.com/DownloadService.ashx?client=CTR_MED_6111&studyid=230&filename=CSR-D0475C00020.pdf

CSR-D0475C00020.pdf

Trial Results Summaries